Mitochondrial DNA Dynamics in Reprogramming to Pluripotency

Alexander J Sercel; Natasha M Carlson; Alexander N Patananan; Michael A Teitell

doi:10.1016/j.tcb.2020.12.009

Mitochondrial DNA Dynamics in Reprogramming to Pluripotency

Trends Cell Biol. 2021 Apr;31(4):311-323. doi: 10.1016/j.tcb.2020.12.009.

Authors

Alexander J Sercel¹, Natasha M Carlson², Alexander N Patananan³, Michael A Teitell⁴

Affiliations

¹ Molecular Biology Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA, USA 90095.
² Department of Biology, California State University Northridge, CA, USA 91330; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA 90095.
³ Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA 90095.
⁴ Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA 90095; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA 90095; California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA, USA 90095; Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, USA 90095; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research University of California, Los Angeles, Los Angeles, CA, USA 90095; Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA 90095; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA 90095. Electronic address: mteitell@mednet.ucla.edu.

Abstract

Mammalian cells, with the exception of erythrocytes, harbor mitochondria, which are organelles that provide energy, intermediate metabolites, and additional activities to sustain cell viability, replication, and function. Mitochondria contain multiple copies of a circular genome called mitochondrial DNA (mtDNA), whose individual sequences are rarely identical (homoplasmy) because of inherited or sporadic mutations that result in multiple mtDNA genotypes (heteroplasmy). Here, we examine potential mechanisms for maintenance or shifts in heteroplasmy that occur in induced pluripotent stem cells (iPSCs) generated by cellular reprogramming, and further discuss manipulations that can alter heteroplasmy to impact stem and differentiated cell performance. This additional insight will assist in developing more robust iPSC-based models of disease and differentiated cell therapies.

Keywords: heteroplasmy; induced pluripotent stem cell; mitochondrial DNA; pluripotency; reprogramming.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Cellular Reprogramming / genetics
DNA, Mitochondrial* / genetics
DNA, Mitochondrial* / metabolism
Induced Pluripotent Stem Cells*
Mitochondria / genetics
Mitochondrial Dynamics

Substances

DNA, Mitochondrial

Abstract

Publication types

MeSH terms

Substances

Grants and funding